Regioselective C(sp2)-C(sp3) Coupling Mediated by Classical and Rollover Cyclometalation

By taking advantage of a sequence of oxidative addition/reductive elimination reactions, Pt(II) cyclometalated derivatives are able to promote a rare C(sp2)-C(sp3) bond coupling, resulting in the production of novel methyl-substituted pyridines and bipyridines. Starting from 6-phenyl-2,2′-bipyridine, the step-by-step full sequence of reactions has been followed, leading to the unprecedented 3-methyl-6-phenyl-2,2′-bipyridine, which was isolated and fully characterized. The synthesis involves the following steps: (1) rollover cyclometalation to give the starting complex [Pt(N^C)(DMSO)Me]; (2) the synthesis of a more electron-rich complex [Pt(N^C)(PPh3)Me] by the substitution of DMSO with triphenylphosphine; (3) oxidative addition with methyl iodide to give the Pt(IV) complex [Pt(N^C)(PPh3)(Me)2(I)]; (4) iodide abstraction with silver tetrafluoborate to give an unstable pentacoordinate intermediate, which rapidly evolves through a carbon–carbon reductive coupling, forming a new C(sp3)-C(sp2) bond; (5) finally, the extrusion and characterization of the newly formed 3-methyl-6-phenyl-2,2′-bipyridine. The reaction has been therefore extended to a well-known classical cyclometalating ligand, 2-phenylpyridine, demonstrating that the method is not restricted to rollover derivatives. Following the same step-by-step procedure, 2-phenylpyridine was converted to 2-o-tolyl-pyridine, displaying the potential application of the method to the larger family of classical cyclometalated complexes. The application of this protocol may be useful to convert an array of heterocyclic compounds to their methyl- or alkyl-substituted analogs.


Introduction
One of the main goals of organometallic chemistry is the functionalization of C−H bonds mediated by transition metals, particularly when it involves the formation of new carbon-carbon bonds [1].The C-C coupling is particularly interesting when it implicates the activation of a C-H bonds in organic compounds followed by metalation (the formation of a metal-carbon bond) and successive functionalization (Scheme 1):

Introduction
One of the main goals of organometallic chemistry is the functionalization of C−H bonds mediated by transition metals, particularly when it involves the formation of new carbon-carbon bonds [1].The C-C coupling is particularly interesting when it implicates the activation of a C-H bonds in organic compounds followed by metalation (the formation of a metal-carbon bond) and successive functionalization (Scheme 1): Scheme 1. Activation, metalation, and functionalization via C-C reductive coupling.
A successive combination of oxidative addition/reductive elimination reactions is often found in catalytic cycles, leading first to the activation of a substrate and second to A successive combination of oxidative addition/reductive elimination reactions is often found in catalytic cycles, leading first to the activation of a substrate and second to the formation of new bonds and hence to newly designed compounds.Reductive elimination is usually the key step in C−C bond formation, representing the reaction in which the final product is formed [2].
The cyclometalation reaction is a useful method for C-H bond activation in aromatic heterocycles, leading to particularly stable organometallic complexes known as cyclometalated compounds [3].These derivatives, characterized by a carbon-heteroatom chelating ligand, have attracted enormous interest for various applications: as catalysts for a large array of reactions [4], in biomedicine as antitumor or antimicrobial agents [5,6], and in the field of innovative materials, such as photoluminescent devices, sensors, switches, etc. [7,8].
Furthermore, after the activation of the C-H bond, the subsequent functionalization of the cyclometalated ligand may facilitate the synthesis of new organic molecules by means of stoichiometric or catalytic processes [9].
Molecules 2024, 29, x FOR PEER REVIEW 2 of 12 the formation of new bonds and hence to newly designed compounds.Reductive elimination is usually the key step in C−C bond formation, representing the reaction in which the final product is formed [2].The cyclometalation reaction is a useful method for C-H bond activation in aromatic heterocycles, leading to particularly stable organometallic complexes known as cyclometalated compounds [3].These derivatives, characterized by a carbon-heteroatom chelating ligand, have attracted enormous interest for various applications: as catalysts for a large array of reactions [4], in biomedicine as antitumor or antimicrobial agents [5,6], and in the field of innovative materials, such as photoluminescent devices, sensors, switches, etc. [7,8].
Furthermore, after the activation of the C-H bond, the subsequent functionalization of the cyclometalated ligand may facilitate the synthesis of new organic molecules by means of stoichiometric or catalytic processes [9].
For these reasons, a great variety of subclasses of cyclometalated species have emerged, particularly for nitrogen donors such as pyridines, imines, and amines.In addition to classical C^N donors (e.g., phenylpyridines and phenylamines), the subclasses of tridentate cyclometalates have been thoroughly studied, comprising N^N^C donors [10] (such as 6-phenyl-2,2′-bipyridine) and the so-called "pincer ligands" [11] (e.g., C^N^C, N^C^N donors).One recent and unusual class is that of the rollover complexes, ref. [12] derived from the internal rotation of bidentate heterocyclic ligands, such as 2,2′bipyridine (Figure 1).Among the various methods, the rollover cyclometalation reaction is a quite new and useful process, suitable for activating heterocyclic donor ligands in remote positions, such as the C3 position in 2,2′-bipyridines (see Figure 1).It is not easy to functionalize these bidentate ligands in certain positions with transition metals owing to their propensity to form stable N^N chelated complexes.In contrast to classical cyclometalated complexes, rollover derivatives contain a free donor atom that confers behaviors not accessible to classical cyclometalated species [13], such as protonation [14], retro-rollover reactions [15,16], successive additional cyclometalation, and polymerization [17].
Rollover complexes were also found to promote C-C bond formation in both stoichiometric (gas phase and in solution) [18,19] and catalytic [20][21][22] reactions.In this regard, we have recently reported that the rollover activation of the C3-H bond in 2,2′bipyridine Pt(II) rollover complexes might be employed to promote C-C bond formation by means of a sequence of oxidative addition and reductive elimination reactions to give methyl-substituted pyridine rings [23].
Following our previous studies in the field [24], we report some aspects of the behavior of one of the most studied organometallic ligands, 6-phenyl-2,2′-bipyridine (bpy Ph ), which lead to the activation and functionalization of the remote pyridine C3-H bond through Pt(II) rollover cyclometalation.The reaction has been successfully extended to the corresponding classical ligand, 2-phenylpyridine (py Ph ), revealing additional potential applications.Among the various methods, the rollover cyclometalation reaction is a quite new and useful process, suitable for activating heterocyclic donor ligands in remote positions, such as the C 3 position in 2,2 ′ -bipyridines (see Figure 1).It is not easy to functionalize these bidentate ligands in certain positions with transition metals owing to their propensity to form stable NˆN chelated complexes.In contrast to classical cyclometalated complexes, rollover derivatives contain a free donor atom that confers behaviors not accessible to classical cyclometalated species [13], such as protonation [14], retro-rollover reactions [15,16], successive additional cyclometalation, and polymerization [17].
Rollover complexes were also found to promote C-C bond formation in both stoichiometric (gas phase and in solution) [18,19] and catalytic [20][21][22] reactions.In this regard, we have recently reported that the rollover activation of the C 3 -H bond in 2,2 ′ -bipyridine Pt(II) rollover complexes might be employed to promote C-C bond formation by means of a sequence of oxidative addition and reductive elimination reactions to give methyl-substituted pyridine rings [23].
Following our previous studies in the field [24], we report some aspects of the behavior of one of the most studied organometallic ligands, 6-phenyl-2,2 ′ -bipyridine (bpy Ph ), which lead to the activation and functionalization of the remote pyridine C 3 -H bond through Pt(II) rollover cyclometalation.The reaction has been successfully extended to the corresponding classical ligand, 2-phenylpyridine (py Ph ), revealing additional potential applications.
The reaction of complex 2 with MeI does not occur easily: under the same conditions followed by analogous cyclometalated Pt(II) complexes (acetone, room temperature), we were not able to obtain the desired Pt(IV) product.The greater difficulty of the oxidative addition reaction on complex 2 may be explained by the donor properties of the rollovercoordinated 6-phenyl-2,2′-bipyridine.As we recently reported [32], a good indicator of the donor properties of platinum(II) cyclometalated complexes is the direct 195 Pt-31 P coupling value revealed by 31 P NMR spectroscopy.In comparison with related cyclometalated ligands (Figure 2), 6-phenyl-2,2′-bipyridine is a poorer donor than cyclometalated 2phenylpyridine and rollover-coordinated 2,2′-bipyridine, but better than the worst donor (6-CF3-2,2′-bipyridine).As a consequence, the platinum center in complex 2 is relatively electron-poor compared with similar cyclometalated complexes and the hampered oxidative addition reaction has a plausible justification. 1 J Pt-P =2105 Hz 1 J Pt-P =2229 Hz 1 J Pt-P =2236 Hz Oxidative addition reactions of alkyl halides to Pt(II) electron-rich complexes have been extensively studied by several authors [26][27][28][29][30].In particular, cyclometalated Pt(II) complexes are known to result in oxidative addition with methyl iodide, affording the corresponding Pt(IV) derivatives [31].The reaction usually proceeds through an intermolecular S N 2 mechanism at room temperature.
The reaction of complex 2 with MeI does not occur easily: under the same conditions followed by analogous cyclometalated Pt(II) complexes (acetone, room temperature), we were not able to obtain the desired Pt(IV) product.The greater difficulty of the oxidative addition reaction on complex 2 may be explained by the donor properties of the rollover-coordinated 6-phenyl-2,2 ′ -bipyridine.As we recently reported [32], a good indicator of the donor properties of platinum(II) cyclometalated complexes is the direct 195 Pt-31 P coupling value revealed by 31 P NMR spectroscopy.In comparison with related cyclometalated ligands (Figure 2), 6-phenyl-2,2 ′ -bipyridine is a poorer donor than cyclometalated 2-phenylpyridine and rollover-coordinated 2,2 ′ -bipyridine, but better than the worst donor (6-CF 3 -2,2 ′ -bipyridine).As a consequence, the platinum center in complex 2 is relatively electron-poor compared with similar cyclometalated complexes and the hampered oxidative addition reaction has a plausible justification.
Oxidative addition reactions of alkyl halides to Pt(II) electron-rich complexes have been extensively studied by several authors [26][27][28][29][30].In particular, cyclometalated Pt(II) complexes are known to result in oxidative addition with methyl iodide, affording the corresponding Pt(IV) derivatives [31].The reaction usually proceeds through an intermolecular SN2 mechanism at room temperature.
The reaction of complex 2 with MeI does not occur easily: under the same conditions followed by analogous cyclometalated Pt(II) complexes (acetone, room temperature), we were not able to obtain the desired Pt(IV) product.The greater difficulty of the oxidative addition reaction on complex 2 may be explained by the donor properties of the rollovercoordinated 6-phenyl-2,2′-bipyridine.As we recently reported [32], a good indicator of the donor properties of platinum(II) cyclometalated complexes is the direct 195 Pt-31 P coupling value revealed by 31 P NMR spectroscopy.In comparison with related cyclometalated ligands (Figure 2), 6-phenyl-2,2′-bipyridine is a poorer donor than cyclometalated 2phenylpyridine and rollover-coordinated 2,2′-bipyridine, but better than the worst donor (6-CF3-2,2′-bipyridine).As a consequence, the platinum center in complex 2 is relatively electron-poor compared with similar cyclometalated complexes and the hampered oxidative addition reaction has a plausible justification.It is likely that the presence of the phenyl substituent slows down the reaction, so we raised the temperature and prolonged the reaction time.In this way, we were able to obtain and isolate the Pt(IV) complex [Pt(bpy Ph -H)I(Me) 2 PPh 3 ], 3, in high yield (Scheme 2).
The reaction of 2 with MeI should give a complex with the methyl and iodide ligands entering in a mutually trans position.However, as previously observed, rapid isomerization produced the more stable isomer, with the phosphane ligand in the axial position with respect to the bipyridine metalated plane [33].
Complex 3 was isolated and characterized analytically and spectroscopically, in particular, by means of NMR spectroscopy.The 31 P NMR spectrum of 3 shows a singlet with satellites at −10.95 ppm, with a Pt-P coupling constant value, 1 J Pt-P = 962.5 Hz, in agreement with a Pt(IV) species, but smaller than that found in the corresponding simple 2,2 ′ -bipyridine rollover complex 3 ′ , [Pt(bpy-H)(Me) 2 I(PPh 3 )] ( 1 J Pt-P = 991 Hz) (Figure 3).position with respect to the bipyridine metalated plane [33].
The 1 H NMR spectrum shows two different coordinated methyls as doublets with satellites due to coupling to 195 Pt and 31 P nuclei.Comparison with NMR data for 3′ shows that the shielded methyl (δ 1.24 ppm, 2 JPt-H = 60.0Hz) is coordinated in the "axial" position (with respect to the bipyridine plane), whereas the deshielded methyl (δ 1.70 ppm, 2 JPt-H = 70.5 Hz) is in the equatorial position.The H6′ signal is strongly deshielded (δ 9.62 ppm, JPt-H ca 11 Hz), as expected, due to proximity to the iodide ligand [34,35].

Treatment of Pt(IV) Complexes with Silver Salts
Compound 3 is stable in the presence of air and moisture, both in the solid state and in solution.
The reaction of 3 with AgBF4 in acetone resulted in the abstraction of the coordinated iodide and the precipitation of solid AgI, which was removed by filtration.The resulting coordinatively unsaturated, five-coordinate species is unstable and rearranges following a reductive elimination process, through C(sp 3 )-C(sp 2 ) coupling, and a subsequent "retrorollover" process, involving the rotation of the substituted pyridine, allows the coordination of the second nitrogen atom to prepare N^N chelated adducts (Scheme 3).On the basis of our previous experience, we expected to obtain the two geometric isomers of the adduct [Pt(N^N)(PPh3)Me] + , as in the case of unsubstituted 2,2′-bipyridine, where the two species 4a′ and 4b′ were isolated in a 1:1 molar ratio (Figure 4).However, The 1 H NMR spectrum shows two different coordinated methyls as doublets with satellites due to coupling to 195 Pt and 31 P nuclei.Comparison with NMR data for 3 ′ shows that the shielded methyl (δ 1.24 ppm, 2 J Pt-H = 60.0Hz) is coordinated in the "axial" position (with respect to the bipyridine plane), whereas the deshielded methyl (δ 1.70 ppm, 2 J Pt-H = 70.5 Hz) is in the equatorial position.The H 6 ′ signal is strongly deshielded (δ 9.62 ppm, J Pt-H ca 11 Hz), as expected, due to proximity to the iodide ligand [34,35].

Treatment of Pt(IV) Complexes with Silver Salts
Compound 3 is stable in the presence of air and moisture, both in the solid state and in solution.
The reaction of 3 with AgBF 4 in acetone resulted in the abstraction of the coordinated iodide and the precipitation of solid AgI, which was removed by filtration.The resulting coordinatively unsaturated, five-coordinate species is unstable and rearranges following a reductive elimination process, through C(sp 3 )-C(sp 2 ) coupling, and a subsequent "retrorollover" process, involving the rotation of the substituted pyridine, allows the coordination of the second nitrogen atom to prepare NˆN chelated adducts (Scheme 3).
It is likely that the presence of the phenyl substituent slows down the reaction, so we raised the temperature and prolonged the reaction time.In this way, we were able to obtain and isolate the Pt(IV) complex [Pt(bpy Ph -H)I(Me)2PPh3], 3, in high yield (Scheme 2).
The reaction of 2 with MeI should give a complex with the methyl and iodide ligands entering in a mutually trans position.However, as previously observed, rapid isomerization produced the more stable isomer, with the phosphane ligand in the axial position with respect to the bipyridine metalated plane [33].
The 1 H NMR spectrum shows two different coordinated methyls as doublets with satellites due to coupling to 195 Pt and 31 P nuclei.Comparison with NMR data for 3′ shows that the shielded methyl (δ 1.24 ppm, 2 JPt-H = 60.0Hz) is coordinated in the "axial" position (with respect to the bipyridine plane), whereas the deshielded methyl (δ 1.70 ppm, 2 JPt-H = 70.5 Hz) is in the equatorial position.The H6′ signal is strongly deshielded (δ 9.62 ppm, JPt-H ca 11 Hz), as expected, due to proximity to the iodide ligand [34,35].

Treatment of Pt(IV) Complexes with Silver Salts
Compound 3 is stable in the presence of air and moisture, both in the solid state and in solution.
The reaction of 3 with AgBF4 in acetone resulted in the abstraction of the coordinated iodide and the precipitation of solid AgI, which was removed by filtration.The resulting coordinatively unsaturated, five-coordinate species is unstable and rearranges following a reductive elimination process, through C(sp 3 )-C(sp 2 ) coupling, and a subsequent "retrorollover" process, involving the rotation of the substituted pyridine, allows the coordination of the second nitrogen atom to prepare N^N chelated adducts (Scheme 3).On the basis of our previous experience, we expected to obtain the two geometric isomers of the adduct [Pt(N^N)(PPh3)Me] + , as in the case of unsubstituted 2,2′-bipyridine, where the two species 4a′ and 4b′ were isolated in a 1:1 molar ratio (Figure 4).However, On the basis of our previous experience, we expected to obtain the two geometric isomers of the adduct [Pt(NˆN)(PPh 3 )Me] + , as in the case of unsubstituted 2,2 ′ -bipyridine, where the two species 4a ′ and 4b ′ were isolated in a 1:1 molar ratio (Figure 4).However, in the case of 6-phenyl-2,2 ′ -bipyridine, likely due to the presence of the bulky phenyl substituent, the situation is more complex.The 1 H NMR spectrum of the isolated product showed a mixture of at least five species in an approximate 8:5:4:2:1 molar ratio (Supplementary Material S3).All species contain a coordinated 3-methyl-6-phenyl-2,2 ′ -bipyridine resulting from the desired C(sp 3 )−C(sp 2 ) coupling, as shown by singlets around 3.0 ppm in a 1:1 molar ratio with the corresponding Pt-CH 3 signals.
in the case of 6-phenyl-2,2′-bipyridine, likely due to the presence of the bulky phenyl substituent, the situation is more complex.The 1 H NMR spectrum of the isolated product showed a mixture of at least five species in an approximate 8:5:4:2:1 molar ratio (Supplementary Material S3).All species contain a coordinated 3-methyl-6-phenyl-2,2′-bipyridine resulting from the desired C(sp 3 )−C(sp 2 ) coupling, as shown by singlets around 3.0 ppm in a 1:1 molar ratio with the corresponding Pt-CH3 signals.A tentative analysis of the complex mixture may explain the signals as follows: two species, present in a relative 4:1 molar ratio (ca 40% and 10% of the total) may be described as the geometric isomers of the adduct [Pt(N^N)(PPh3)Me] + (N^N = 3-methyl-6-phenyl-2,2′-bipyridine, 4a and 4b).This interpretation is based on the presence of two coordinated methyls appearing as doublets with satellites, due to coupling with 195 Pt and 31 P nuclei: one of the signals, corresponding to the major species, is highly shielded (4a, ca 40%, δ −0.48 ppm, JP-H = 3.8 Hz, JPt-H = 69.5 Hz) as it is in proximity of the shielding cone of the phenyl substituent of the bipyridine, whereas the other signal (4b, ca 10%, δ 0.86 ppm, JP-H = 3.6 Hz, JPt-H = ca 70 Hz) appears in the usual region at around 0.9-1.1 ppm.Two singlets, at 2.99 and 3.07 ppm, with the same integral values and 4:1 molar ratio, may be assigned to the methyls on the C3 position in the central pyridine ring.In the 31 P NMR spectrum, these species gave singlets with satellites at 17.57 ppm (4a, JPt-P = 4581 Hz) and 12.49 ppm (4b, JPt-P = 4397 Hz), with the same 4:1 molar ratio.Other smaller signals in the 31 P NMR spectrum, e.g., a singlet at 31.72 ppm, were not interpreted.
In the 1 H NMR spectrum, two other compounds, 4c and 4d, in an approximate 5:4 molar ratio, (ca.25% and 20% of the total, respectively), may tentatively be described as solvato species [Pt(N^N)(S)Me] + (S = acetone or water) generated from detachment of the PPh3 ligand; these species show two singlets with satellites, indicating the absence of coordinated PPh3 (4c, 25%: δ 1.04 ppm, JPt-H = 71.5 Hz; 4d, 20%: δ 0.96 ppm, JPt-H = 67.5 Hz).Two singlets at 2.63 and 2.88 ppm (4c and 4d respectively, Me on C3) indicates that also these species are derived from the C-C coupling.Furthermore, two signals at 3.80 and 2.19 ppm (the latter overlapping with free acetone) may support the assignment of 4c and 4d as solvato species.Finally, a small singlet with satellites, at −0.17 ppm (ca.5%, JPt-H = 66.5 Hz), may be a solvato species (4e) with a methyl coordinated close to the phenyl substituent.A tentative analysis of the complex mixture may explain the signals as follows: two species, present in a relative 4:1 molar ratio (ca 40% and 10% of the total) may be described as the geometric isomers of the adduct [Pt(NˆN)(PPh 3 )Me] + (NˆN = 3-methyl-6-phenyl-2,2 ′ -bipyridine, 4a and 4b).This interpretation is based on the presence of two coordinated methyls appearing as doublets with satellites, due to coupling with 195 Pt and 31 P nuclei: one of the signals, corresponding to the major species, is highly shielded (4a, ca 40%, δ −0.48 ppm, J P-H = 3.8 Hz, J Pt-H = 69.5 Hz) as it is in proximity of the shielding cone of the phenyl substituent of the bipyridine, whereas the other signal (4b, ca 10%, δ 0.86 ppm, J P-H = 3.6 Hz, J Pt-H = ca 70 Hz) appears in the usual region at around 0.9-1.1 ppm.Two singlets, at 2.99 and 3.07 ppm, with the same integral values and 4:1 molar ratio, may be assigned to the methyls on the C 3 position in the central pyridine ring.In the 31 P NMR spectrum, these species gave singlets with satellites at 17.57 ppm (4a, J Pt-P = 4581 Hz) and 12.49 ppm (4b, J Pt-P = 4397 Hz), with the same 4:1 molar ratio.Other smaller signals in the 31 P NMR spectrum, e.g., a singlet at 31.72 ppm, were not interpreted.
In the 1 H NMR spectrum, two other compounds, 4c and 4d, in an approximate 5:4 molar ratio, (ca.25% and 20% of the total, respectively), may tentatively be described as solvato species [Pt(NˆN)(S)Me] + (S = acetone or water) generated from detachment of the PPh 3 ligand; these species show two singlets with satellites, indicating the absence of coordinated PPh 3 (4c, 25%: δ 1.04 ppm, J Pt-H = 71.5 Hz; 4d, 20%: δ 0.96 ppm, J Pt-H = 67.5 Hz).Two singlets at 2.63 and 2.88 ppm (4c and 4d respectively, Me on C 3 ) indicates that also these species are derived from the C-C coupling.Furthermore, two signals at 3.80 and 2.19 ppm (the latter overlapping with free acetone) may support the assignment of 4c and 4d as solvato species.Finally, a small singlet with satellites, at −0.17 ppm (ca.5%, J Pt-H = 66.5 Hz), may be a solvato species (4e) with a methyl coordinated close to the phenyl substituent.
Here, our main interest consisted in the isolation of the new 3-methyl-6-phenyl-2,2 ′bipyridine, so we did not devote further efforts to the characterization of species 4a-e, and proceeded with the decomplexation of the ligand from the metal.
The free-substituted 2,2 ′ -bipyridine 5 was isolated by reaction of the 4a-e species with dppe (1,2-bis-diphenylphosphinoethane).The chelating diphosphane easily displaces the bipyridine ligand so that the organic species can be isolated in good yield (ca. 80%) and analyzed.
To the best of our knowledge, compound 5 has not previously appeared in the literature and its synthesis is unprecedented.For this reason, we performed a thorough characterization in solution by means of mono-and two-dimensional 1 H and 13 C NMR spectroscopy ( 1 H, 13

C, H-H COSY, H-H NOESY, H-C HMQC, H-C HMBC).
The 1 H and 13 C NMR spectra clearly show the methyl in position 3 ( 1 H, 2.58 ppm, 13 C, 19.98 ppm).The aromatic region shows all the expected hydrogens, with 4, 2, and 5-proton spin systems for the aromatic rings, for which a COSY H-H spectrum allowed the assignment of all 1 H NMR signals.
In addition, 1 H- 13 C HSQC and HMBC spectra allowed the assignment of 13 C signals.A complete assignment is reported in Figure 5.
Here, our main interest consisted in the isolation of the new 3-methyl-6-phenyl-2,2′bipyridine, so we did not devote further efforts to the characterization of species 4a-e, and proceeded with the decomplexation of the ligand from the metal.
The free-substituted 2,2′-bipyridine 5 was isolated by reaction of the 4a-e species with dppe (1,2-bis-diphenylphosphinoethane).The chelating diphosphane easily displaces the bipyridine ligand so that the organic species can be isolated in good yield (ca. 80%) and analyzed.
To the best of our knowledge, compound 5 has not previously appeared in the literature and its synthesis is unprecedented.For this reason, we performed a thorough characterization in solution by means of mono-and two-dimensional 1 H and 13 C NMR spectroscopy ( 1 H, 13

C, H-H COSY, H-H NOESY, H-C HMQC, H-C HMBC).
The 1 H and 13 C NMR spectra clearly show the methyl in position 3 ( 1 H, 2.58 ppm, 13 C, 19.98 ppm).The aromatic region shows all the expected hydrogens, with 4, 2, and 5-proton spin systems for the aromatic rings, for which a COSY H-H spectrum allowed the assignment of all 1 H NMR signals.
In addition, 1 H- 13 C HSQC and HMBC spectra allowed the assignment of 13 C signals.A complete assignment is reported in Figure 5.In particular, the 2D 1 H- 13 C HMBC NMR spectrum provided fundamental information, revealing intense cross peaks for 3 J(C-H) coupling, as well as weak peaks for 2 J(C-H) and 4 J(C-H) couplings.As an example, the 1 H methyl singlet at 2.58 ppm shows cross peaks with signals at 155.52 (C2), 130.9 (C3), and 140.16 (C4) ppm, supporting the given formulation.The analysis of the other peaks allowed complete assignment.The bonding  In particular, the 2D 1 H- 13 C HMBC NMR spectrum provided fundamental information, revealing intense cross peaks for 3 J(C-H) coupling, as well as weak peaks for 2 J(C-H) and 4 J(C-H) couplings.As an example, the 1 H methyl singlet at 2.58 ppm shows cross peaks with signals at 155.52 (C 2 ), 130.9 (C 3 ), and 140.16 (C 4 ) ppm, supporting the given formulation.The analysis of the other peaks allowed complete assignment.The bonding of the methyl group on the C 3 position is confirmed by the 2D COSY spectrum, which shows a weak longrange interaction between the methyl protons at 2.58 ppm and the H 4 signal at 7.70 ppm (part of an AB system with the H 5 hydrogen).
The 1 H NMR spectrum of 5 in CD 2 Cl 2 slightly separated the H 4 and H 5 signals in the AB system (δ 7.73, 7.75 ppm, J AB = 8.1 Hz).A NOESY spectrum showed NOE contacts between the AB system and the methyl at 2.60 ppm, as well as with the H 2" protons; a detailed analysis, hampered by the tightness of the AB system, allowed assignment of the H 4 and H 5 signals (δ 7.73 and 7.75 ppm, respectively).
Functionalization in the C 3 position of 2,2 ′ -bipyridines is not so common: the methods reported in literature comprise Negishi [44] and Suzuki-Miyaura coupling [45], in addition to co-cyclotrimerization reactions [46].In our previous investigation, we reported that only rollover complexes were able to follow the sequence of reactions also reported in this paper.The intermediate adducts [Pt(NˆN)(PPh 3 )Me] + , analogous to 4a-e, were stabilized by chelation, a behavior not available for classical ligands such as 2-phenylpyridine.However, the retro-rollover process should follow the C-C coupling, so we analyzed in more detail the reaction starting from the classical analog [Pt(NˆC)Me(PPh 3 )] complex derived from 2-phenylpyridine, 6 (Scheme 4).
shows a weak long-range interaction between the methyl protons at 2.58 ppm and the H4 signal at 7.70 ppm (part of an AB system with the H5 hydrogen).
The 1 H NMR spectrum of 5 in CD2Cl2 slightly separated the H4 and H5 signals in the AB system (δ 7.73, 7.75 ppm, JAB = 8.1 Hz).A NOESY spectrum showed NOE contacts between the AB system and the methyl at 2.60 ppm, as well as with the H2" protons; a detailed analysis, hampered by the tightness of the AB system, allowed assignment of the H4 and H5 signals (δ 7.73 and 7.75 ppm, respectively).
Functionalization in the C3 position of 2,2′-bipyridines is not so common: the methods reported in literature comprise Negishi [44] and Suzuki-Miyaura coupling [45], in addition to co-cyclotrimerization reactions [46].In our previous investigation, we reported that only rollover complexes were able to follow the sequence of reactions also reported in this paper.The intermediate adducts [Pt(N^N)(PPh3)Me] + , analogous to 4a-e, were stabilized by chelation, a behavior not available for classical ligands such as 2-phenylpyridine.However, the retro-rollover process should follow the C-C coupling, so we analyzed in more detail the reaction starting from the classical analog [Pt(N^C)Me(PPh3)] complex derived from 2-phenylpyridine, 6 (Scheme 4).
Following the same reaction sequence used for 1-4, we obtained the Pt(IV) species 3a, which was isolated in the solid state and analyzed by means of NMR spectroscopy.In this case, we did not try to isolate adduct species analogous to 4a-e, as we were mainly interested in the isolation of the final organic compound.Owing to the different solubility of 3a with respect to 3, the reaction with silver tetrafluoborate was performed in a CH2Cl2/acetone 5/1 molar ratio mixture.Analogous to the previous case, the addition of AgBF4 followed by displacement with dppe, 1,2-bis(diphenylphosphine)ethane, led to the isolation of 2-ortho-tolylpyridine, 6, derived from the C(sp 3 )-C(sp 2 ) coupling.Compound 6 was purified by acid-base extraction and characterized by NMR spectroscopy.The spectroscopic data, in agreement with the previously reported data for 6, ref. [47] revealed, inter alia, the presence of the methyl group at 2.41 and 20.26 ppm, in the 1 H and 13 C spectra, respectively.
Furthermore, the GC-MS spectrum (EI) shows peaks at m/z 168.Following the same reaction sequence used for 1-4, we obtained the Pt(IV) species 3a, which was isolated in the solid state and analyzed by means of NMR spectroscopy.
In this case, we did not try to isolate adduct species analogous to 4a-e, as we were mainly interested in the isolation of the final organic compound.Owing to the different solubility of 3a with respect to 3, the reaction with silver tetrafluoborate was performed in a CH 2 Cl 2 /acetone 5/1 molar ratio mixture.Analogous to the previous case, the addition of AgBF 4 followed by displacement with dppe, 1,2-bis(diphenylphosphine)ethane, led to the isolation of 2-ortho-tolylpyridine, 6, derived from the C(sp 3 )-C(sp 2 ) coupling.Compound 6 was purified by acid-base extraction and characterized by NMR spectroscopy.The spectroscopic data, in agreement with the previously reported data for 6, ref. [47] revealed, inter alia, the presence of the methyl group at 2.41 and 20.26 ppm, in the 1 H and 13 C spectra, respectively.
The obtained result is significant because, to the best of our knowledge, this is a new strategy for C-C coupling in a classical cyclometalated complex, following this sequence of reactions.Moreover, this result suggests the possibility of extending the functionalization to a wide range of cyclometalated ligands.

Experimental Section
All the solvents were purified and dried according to standard procedures [48].Cis-[Pt(DMSO) 2 (Me) 2 ] was synthesized according to reference [49,50].Elemental analyses were performed with a PerkinElmer elemental analyzer 240B. 1 H, 13 C{ 1 H}, and 31 P{ 1 H} NMR spectra were recorded using a Bruker Avance III 400 spectrometer operating at 400.132, 100.623 and 161.967MHz, respectively.Chemical shifts are given in ppm relative to internal TMS for 1 H and 13 C{ 1 H} and external 85% H 3 PO 4 for 31 P{ 1 H}; J values are given in Hz. 1 H-1 H COSY, 1 H-1 H NOESY, 1 H-13 C HSQC, and 1 H- 13 C HMBC experiments were performed by means of standard pulse sequences.

Preparations
Synthesis of 2, [Pt(bpy Ph -H)Me(PPh 3 )] Complex 2 was obtained as previously reported [20], following a one-pot procedure, adding PPh 3 after completion of the reaction between cis-[Pt(DMSO) 2 (Me) 2 ] and 6-phenyl-2,2 ′ -bipyridine to give complex 1 as an intermediate.Yield 95%. 1   To a solution of 3 (255.3mg; 0.30 mmol) in acetone (20 mL) AgBF 4 (61.4 mg; 0.30 mmol) was added under stirring at room temperature in an argon atmosphere.After three hours, the formed AgI was removed by filtration over celite.The filtered solution was concentrated to a small volume and treated with a hexane-diethyl ether 1:5 mixture to give a precipitate that was filtered off and dried to give the analytical sample.